Total First-Year Costs of Acute Coronary Syndrome in a Managed Care Setting

OBJECTIVES: There is a limited amount of literature examining the burden and cost of illness of acute coronary syndrome (ACS) in the managed care population. The goal of this study was to estimate the total cost of health care utilization (health plan plus patient) in the 12-month period following newly onset ACS. The demographic and health characteristics of these patients are compared with the similar data from 2 large clinical trials: CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) and PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy Thrombolysis in Myocardial Infarction 22). METHODS: A retrospective claims analysis was conducted for the 2-year period from July 1, 1999, through June 30, 2001. ACS was defined as an emergency room visit or hospitalization with a primary International Classification of Diseases, 9th Edition/Revision (ICD-9) diagnosis of 410.xx (acute myocardial infarction) or 411.1x (intermediate coronary syndrome). Patients were required to be free of any ACS claim in the previous 6 months. Patients without 6 months of prior continuous enrollment or those patients younger than 18 years were excluded. Patients were followed up to 12 months to identify total medical and pharmacy costs, revascularization procedures, and medication use. RESULTS: A total of 13,731 patients met the inclusion criteria, yielding 133,814 months of follow-up (mean: 9.75 months per patient) and representing approximately 0.4% of the managed care members in the database during the study period. The mean age was 54 years and 68% were male. The total direct cost incurred by the health plan and patients was $309 million ($2,312 per patient month of follow-up); 72% of total costs were attributable to hospitalizations. The majority of costs were medical ($286 million, 93%), and $23 million (7%) were pharmacy costs. Fifty-one percent of patients had a revascularization procedure, which was typically performed during the index hospitalization (median time to revascularization was 0 days). Coronary artery stent implantation was the most common revascularization procedure (68%). During follow-up, 490 patients (3.6%) had a detectable death, 58% of patients received a beta-blocker, 60% received one or more cholesterol-lowering medications, and 36% of patients received clopidogrel therapy. Aspirin therapy was not measured. CONCLUSIONS: These managed-care patients with newly onset ACS incurred substantial costs in the 12 months following initial presentation. Revascularization was a common therapeutic intervention for these patients. There appear to be opportunities to improve medication therapy after an acute ACS event. There were some demographic and health characteristics that were different in these commercially insured patients from those in 2 large clinical trials.

METHODS: A retrospective claims analysis was conducted for the 2-year period from July 1, 1999, through June 30, 2001. ACS was defined as an emergency room visit or hospitalization with a primary International Classification of Diseases, 9th Edition/Revision (ICD-9) diagnosis of 410.xx (acute myocardial infarction) or 411.1x (intermediate coronary syndrome). Patients were required to be free of any ACS claim in the previous 6 months. Patients without 6 months of prior continuous enrollment or those patients younger than 18 years were excluded. Patients were followed up to 12 months to identify total medical and pharmacy costs, revascularization procedures, and medication use.
RESULTS: A total of 13,731 patients met the inclusion criteria, yielding 133,814 months of follow-up (mean: 9.75 months per patient) and representing approximately 0.4% of the managed care members in the database during the study period. The mean age was 54 years and 68% were male. The total direct cost incurred by the health plan and patients was $309 million ($2,312 per patientmonth of follow-up); 72% of total costs were attri butable to hospitalizations. The majority of costs were medical ($286 million, 93%), and $23 million (7%) were pharmacy costs. Fifty-one percent of patients had a revascularization procedure, which was typically performed during the index hospitalization (median time to revascularization was 0 days). Coronary artery stent implantation was the most common revascularization procedure (68%). During follow-up, 490 patients (3.6%) had a detectable death, 58% of patients received a beta-blocker, 60% received one or more cholesterol-lowering medications, and 36% of patients received clopidogrel therapy. Aspirin therapy was not measured.
CONCLUSIONS: These managed-care patients with newly onset ACS incurred substantial costs in the 12 months following initial presentation. Reva s c u l a r i z a t i o n was a common therapeutic intervention for these patients. There appear to be opportunities to improve medication therapy after an acute ACS event. There were some demographic and health characteristics that were different in these commercially insured patients from those in 2 large clinical trials.

Total First-Year Costs of Acute Coronary Syndrome in a Managed Care Setting
members was enrolled in Medicare + Choice (now known as Medicare Advantage) plans. Patients were identified during the time period from July 1, 1999, through June 30, 2001, (patient selection period). The 6-month period prior to entry into the study (baseline period) was examined for previous diagnoses of ACS and prior medication use. Patients were followed until they disenrolled from the health plan, a death was noted in the medical claims, or for up to 12 months following study entry (whichever occurred first). The study period for each patient included all claims incurred during the 6-month baseline period and the variable-length follow-up period. The follow-up period included all claims incurred during the index event through the end of the study period.

Patient Identification
This study included enrollees of geographically diverse commercial health plans that are part of a national MCO. The health plans are fee-for-service models in which claims from health care providers are submitted directly to the plan for payment.
The study population included patients who were seen in an emergency room (ER) or hospitalized during the time period of July 1, 1999 . We did not include code 411.8 (acute ischemic heart disease not elsewhere classified) or 411.81 (coro n a ry occlusion without MI) or 411.89 (acute ischemic heart disease not elsewhere classified). The first ER visit or hospitalization for MI or UA during the patient selection period was designated as the index event. Patients were included in the study if they had at least 6 months of continuous eligibility prior to their index event, were aged 18 years or older, and did not have any claims with an ACS diagnosis during the baseline period.

Patient Characteristics/Outcomes Measured Comorbidities
Patient comorbidities were identified using ICD-9 codes from medical claims during the entire study period. The University of Washington Diagnostic Clusters were used to group diagnosis codes for identification of comorbidities. 10 The Washington Clusters methodology involves categorization of comorbidities with standardized definitions. For example, this method classifies "lipid disorders" as ICD-9 codes 272.0-272.9, which allows greater transparency for analysis purposes and for comparing studies with one another.

Revascularization Procedures
Patients were classified as having received percutaneous transluminal coronary angioplasty (PTCA), stent implantation, or coronary artery bypass graft (CABG) during the follow-up period. Pro c e d u res were identified using the following ICD-9/common procedural terminology codes: PTCA-36.01, 36.02, 36.05, 92982; stent-36.06, 36.07, 92980; CABG-36.1x, 33510-33514, 33516, 33533-33536. The type of the first revascularization was recorded as well as the number of days from the index event until the first revascularization. For patients with more than one type of revascularization on the same day, the "first" revascularization was designated using a hierarchy of CABG, stent, and then PTCA.

Utilization and Cost
The total number and cost of health services utilized during the follow-up period (including the index event) were determined for each patient. Medical utilization was categorized into hospitalizations, office/outpatient visits, ER visits, lab services, nursing home visits, and surgery center visits based on the site of service, type of provider, or procedure that was coded on the claim. In addition, the total cost (to the health plan and patient) of all pharmacy claims during the follow-up period was determined. For each type of utilization, cost was calculated as that incurred by the plan and the patient, determined from the amount paid by the health plan plus any copayments or deductibles paid by patient. Costs are expressed in 1999-2001 U.S. dollars.

ACS-Related Pharmacotherapy
The use of medications related to ACS was also measured. The receipt of at least one prescription in each of the following classes during the baseline identification and follow-up periods w e re re c o rded for each patient: nonstatin lipid-lowering therapy, HMG Co-A reductase inhibitor (statin), beta-blocker, ACE inhibitor, angiotensin II receptor blocker, calcium channel blocker, and clopidogrel. Data on aspirin utilization was unavailable because of its nonprescription status. The length of clopidogrel therapy was defined as the number of days between the first clopidogrel prescription in the follow-up period through the run-out date (date of fill plus the days supplied) of the last prescription. Patients were designated as newly initiating therapy during the follow-up period if they did not receive a prescription in the same drug class during the baseline identification period; otherwise, they were designated as continuing therapy. The total number of patients receiving therapy is the number of "new" plus "continuing" users.

Analyses
All analyses are descriptive in nature. For categorical variables, the number of patients with each attribute per patient-month of follow-up is given. For continuous variables, the mean p e r-patient-month was calculated. Because of the high pro p o rt i o n ( 6 4 % ) of patients with the full 365 days of follow-up, the overall percentages and mean values are also presented.

Study Population
Of the 21,291 patients identified as having at least one ACS inpatient or ER claim during the identification period, 13,731 (64.5%) patients met the inclusion criteria (Table 1), providing a total of 133,814 months of follow-up (mean = 9.75 months). The average number of days of follow-up for the entire sample was 292 days. Only 91 patients had 0 days of follow-up, while 8,730 (64%) of patients had the entire 365 days of follow-up. During the follow-up period, 490 patients (3.6%) died and 4,511 (32.9%) disenrolled. Table 2 provides characteristics of the study sample. The majority of patients were male (68.2%) and between the ages of 45 and 64 years (72.6%). The mean age of the study population was 54.2 years.
A total of 51.7% of study patients had an index diagnosis of UA, and 48.3% had an index diagnosis of MI. The majority of patients entered the study through an inpatient stay (85%) v e r s u s an ER visit (15%).
Medication use in the baseline period (pre-ACS event) indicated an awareness and treatment of cardiovascular risk factors for a portion of the population. Twenty-two percent of patients had at least one beta-blocker claim in the baseline period, 19% of patients had a claim for an ACE inhibitor, and more than 30% had at least one claim for a cholesterol-lowering medication.
The average number of comorbidities using the Washington Clusters method was 12.7. Overall, 10,083 patients (73%) had a diagnosis of hypertension, and 10,010 (73%) had a diagnosis of lipid disorders. In addition, approximately 30% of patients had a diagnosis of diabetes mellitus, and approximately 30% had a diagnosis of alcohol and drug abuse (including smoking). The presence of comorbidities was detected at any time during the baseline and follow-up period, and the high rates of diagnoses may be a result of the contact with the health care system due to the ACS event.

Revascularization Rates and Health Services Utilization Cost
A p p roximately 51% of patients had at least one re v a s c u l a r i z a t i o n procedure during the follow-up. The distribution of the first revascularization procedure is shown in Table 3. The majority of patients received a stent as the first procedure (34%). While the mean time to revascularization was 7.5 days for all procedures combined, the median was 0 days, indicating that a majority of patients received their revascularization on their index date. Overall, 69% of patients receiving a re v a s c u l a r i z a t i o n had the procedure on their index date. A small number of patients (2.4%) received a PTCA procedure as their first revascularization, with a mean time to revascularization of 13 days; however, the median time to revascularization was the same as the other procedures at 0 days.
Total health care costs for all 13,731 patients during the followu p period were approximately $309 million or $22,529 per patient or $2,312 per patient-month ( Table 4). The largest component of cost was hospitalizations, which accounted for 71% ($221 million) of expenditures. Nearly all patients (93%) had at least one hospitalization during the study period, and the mean number of hospital days per patient-month was 0.65. A total of 3,641 patients (26.5%) had more than one hospitalization, and there were 6,770 hospitalizations after the index event.
The second largest cost component was office/outpatient visits, accounting for approximately $37 million (Table 4). Twenty-four percent of the cost was for cardiologist visits, 8.5% was for general practitioner visits, 7.0% was for internist visits,

Medication Use in the Follow-up
A majority of patients received a cholesterol-lowering medication during follow-up (55.9% received a statin, 10.3% a nonstatin cholesterol medication). Overall, 58.4% of patients received a p rescription for a beta-blocker, 37.6% received an ACE inhibitor, 6.9% received an angiotensin-2 blocker, and 24.2% received a calcium channel blocker (Figure 1). Approximately 36% of patients received a prescription for the antiplatelet drug clopidogrel during the follow-up period, with the vast majority (95%) newly initiating therapy (Figure 1). The mean length of clopidogrel therapy during the follow-up period was 92 days and the median was 30 days. The average length of follow-up for clopidogrel users was 308 days.

■■ Discussion
Attention to cardiovascular risk factors to avoid serious events such as ACS are discussed in the American Heart Association 2002 guideline for the primary prevention of cardiovascular disease and stroke. The guideline provides treatment recommendations for smoking cessation, blood pre s s u re contro l , aspirin use, blood lipid management, diabetes management, etc., which are fundamental to reducing clinically serious and costly first events. 11 To our knowledge, this is the most contemporary and largest cost-of-illness study of ACS in a managed care setting. As such, it provides data on inpatient and outpatient resource utilization, including outpatient drug use. Since many of the national statistics indicate the largest burden of illness is in those patients over age 65, 2 the data in this study of a younger MCO population show a substantial cost of illness for these MCO patients as well as a high number of comorbidities.
Several demographic comparisons of our data with 2 recent clinical trials in ACS may be useful and are represented in Table  5. The comparators were the Clopidogrel in Unstable Angina to    Prevent Recurrent Events (CURE) trial, 12 and the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial. 13 CURE studied the effects of clopidogrel plus aspirin compared with aspirin alone in more than 12,000 patients with ACS, with a mean follow-up of 9 months. Thus, CURE was one of the largest single trials of ACS. The efficacy end point in the CURE clinical trial was the composite of death, MI, and stroke, which occurred in 9.3% of patients on combination therapy with clopidogrel and aspirin versus 11.4% for patients on aspirin alone (risk reduction [RR] = 0.80; 95% confidence interval [CI], 0.72-0.90; P < 0.001).

P o p u l a t i o n % of M o n t h R e v a s c u l a r i z a t i o n R e v a s c u l a r i z a t i o n N= 1 3 , 7 3 1 P a t i e n t s N= 1 3 3 , 8 1 4 ( D a y s ) ( D a y s )
The PROVE IT-TIMI 22 study enrolled more than 4,000 ACS patients (primarily from the United States) for an average follow-up of 24 months. The goal of PROVE IT-TIMI 22 was to c o m p a re the effects of pravastatin and atorvastatin on c a rdiovascular events. The efficacy end point was the composite of death, MI, stroke, or UA requiring hospitalization or revascularization, which occurred in 26.3% of patients on pravastatin therapy and 22.4% of those on atorvastatin (RR = 16%; 95% CI, 5%-26%; P = 0.005). As seen in Table 5, there were several d i ff e rences apparent between the studies, including the proportion of patients who had diabetes, hypertension, an index diagnosis of UA, and the number who underwent a revascularization during the course of follow-up. Not shown in Table 5 is the conduct of the CURE trial among patients primarily outside the United States.
It is interesting to note the number of patients who were excluded from the current study due to an ACS claim in the 6-month prestudy period (Table 1). These 1,819 patients (8.5% of the total sample) provide additional insight into the re c u rrence rate of events requiring ER or hospitalization admission in a real-world setting (i.e., not in a clinical trial). It is also important to note the relatively high proportion of patients with more than one inpatient stay during the study period (26.5%). This is an area that warrants further examination by both clinicians and health plans to understand the nature of these readmissions and determine if measures can be implemented to reduce this figure.
Considering costs of care to a health plan, Ray et al. examined data from the Kaiser Permanente Medical Care program in 1995-1996 and found that ischemic heart disease was re s p o n s i b l e for 6.8% of total health plan costs after adjusting for age, gender, and comorbidities. 14 While the actual costs are difficult to compare with the current study, given the different inclusion criteria, the cost breakdown was 82% hospital, 13% clinic, and 4% pharmacy, which is somewhat similar to our findings. In the c u rrent study, total health care costs were more than $300 million and distributed as pharmacy 7% and medical 93% (inpatient 72%, outpatient 12%, other medical 9%). The majority of medical cost was attributable to the index hospitalization.
The mean total costs during the first year after the event Health Services Utilization and Cost in the Follow-up Period*  were $22,528 per ACS patient, which compares with the inflation-adjusted estimate of direct medical costs of $14,011 to $20,372 by Russell et al. 8 and $17,292 by Bloom et al. 9 Not surprisingly, a general link of disease severity to costs was seen since patients with UA had somewhat lower index episode costs compared with patients with acute MI. Again, our data may be m o re reflective of the current trend for more aggressive intervention and revascularization in the United States. The effect of early revascularization on long-term costs is under further study.
These managed care ACS patients are also frequent users of outpatient provider services, with 1.75 office/outpatient visits per patient-month. Cardiologist visits were the most frequent provider type, but the sum of visits for general practitioner plus internists was larger than cardiologist visits alone over the first year.
Total mean pharmacy costs were $1,820 ($173 PPPM), but these costs are difficult to compare with earlier studies, given the number of new pharmaceuticals introduced over the past several years. It is also important to note these pharmacy costs in relation to the probable underutilization of several drugs that are widely recommended for secondary prevention. Thus, this dollar value may or may not be an appropriate benchmark value.
Drug therapy according to practice guidelines appears to still have room for improvement. Figure 1 generally suggests some level of underutilization for cholesterol-lowering drugs, beta-blockers, ACE inhibitors, and clopidogrel. Patients classified as "continuing users" were those on medications of interest prior to the index event. As seen in Table 2 and Figure 1, there was a high pro p o rtion of patients who may have been unrecognized (not on medication for known risk factors) prior to the index event.
For the antiplatelet clopidogrel, there was a relatively short duration of treatment, suggesting that much of the use may have been in the stent patient. In 2002, the American Heart Association/American College of Cardiology suggested treating patients with ACS for 1 to 9 months with clopidogrel. 15 More recent guidelines for PCI patients suggest a longer duration of clopidogrel therapy. 16 Our data precede these guidelines somewhat and should be reexamined by others using more current administrative claims data. There is also emerging literature re g a rding potential drug interactions with clopidogre l 1 7 although the topic is controversial. 18 Because of the large number of comorbidities and concomitant medications in these patients, this topic also deserves further study in the usual care setting, outside of clinical trials.

Limitations
As with any claims database study, miscoding of medical claims and missing data are possible. Patients with dual insurance coverage may have another third-party payer that incurred some costs for services rendered. We could not measure the use of aspirin in ACS patients since over-the-counter medications are not captured in administrative claims data. We also did not attempt to measure indirect costs or the societal burden of ACS. However, this study examines the total direct medical costs incurred by a health plan and its members associated with ACS over 12 months of follow-up.

■■ Conclusion
These data demonstrate a substantial cost to treat ACS in a managed care health plan whose members are typically younger than in a population-based group. These managed care patients have a high number of comorbid medical conditions. Early revascularization appears to be a common therapeutic interv e n t i o n , occurring in about one half of these patients. Total health care costs (health plan plus patient) were dominated by medical costs, most of which occurred during the index hospitalization. Drug therapy according to newer practice guidelines probably still has room for improvement, which is a typical finding in studies that are not controlled clinical trials. Further research is warranted to predict which patients may be high utilizers of services, to examine further the costs of revascularization since it was a common therapeutic strategy, and to compare the costs of ACS with the costs of other illnesses.

DISCLOSURES
These study results were presented, in part, on April 2, 2004, as a poster at the Academy of Managed Care Pharm a c y ' s 16th Annual Meeting & Showcase in San Francisco, California. Funding for this re s e a rch was provided by Eli Lilly and Company and obtained by author Patrick L. McCollam, who is an employee and s h a reholder of Lilly; author Lida R. Etemad is employed by Ingenix, Inc., which has received funding for re s e a rch from numerous pharmaceutical companies.
Etamad served as principal author of the study. Study concept and design, analysis and interpretation of data, drafting of the manuscript and its critical Selected Characteristics of CURE, PROVE IT-TIMI 22, and Current Study revision, and statistical expertise were contributed by both authors. Administrative, technical, and/or material support was provided by Jay Meyer, PhD, at Ingenix and Lee Bowman, PhD, at Eli Lilly and Company.